New exploratory data from the phase 2 DAZALS trial (NCT05407324) showed that patients with amyotrophic lateral sclerosis (ALS) who received 300 mg/day of dazucorilan (Corcept Therapeutics), an investigational oral selective glucocorticoid receptor modulator, had an 87% lower risk of death over 2 years than patients who received placebo only.¹

Findings also showed that patients treated with dazucorilan had significantly reduced serum inflammatory markers after 24 weeks. Lead author Shafeeq Ladha, MD, director of the Gregory W. Fulton ALS and Neuromuscular Center at Barrow Neurological Institute in Phoenix, Arizona, presented the analysis at the 2026 Network of Excellence for ALS (NEALS) Annual Meeting, held October 27-30, 2026, in Clearwater, Florida.

Study Overview and Key Findings

DAZALS enrolled adults with sporadic or familial ALS and a TRICALS risk profile score of –6 to –3. Participants were randomly assigned 1:1:1 to dazucorilant 300 mg/day (n = 83), dazucorilant 150 mg/day (n = 83), or placebo (n = 82) for 24 weeks. After the double-blind period, participants could enter a 132-week open-label extension (OLE) of dazucorilant 300 mg/day. The current analysis reported 2-year overall survival (OS) and inflammatory biomarker data.

As of April 16, 2026, 81 deaths had been reported. By original assignment, deaths occurred in 26.5% of the 300-mg group, 32.5% of the 150-mg group, and 39.0% of the placebo group. In exploratory 2-year analyses, participants assigned to dazucorilant 300 mg/day had a lower risk of death than placebo recipients who did not cross over to dazucorilant in the OLE (n = 18) (HR, 0.13; 95% CI, 0.05-0.35; P <.0001).

Participants who received the 300-mg dose for more than 24 weeks (n = 51) also had a lower risk of death than those who received dazucorilant 150 mg/day or placebo only for 24 weeks (n = 29) (HR, 0.39; 95% CI, 0.17-0.92; P = .0305). The survival benefit held regardless of whether baseline neurofilament light chain levels were below or at or above the median.

After 24 weeks of treatment with the 300-mg dose, serum monocyte chemoattractant protein 1 levels were significantly reduced (P = .0080). Macrophage inflammatory protein 1β showed a modest but significant reduction (P = .0450). Neither marker changed significantly in the placebo group. In the OLE, the most common treatment-emergent adverse events were abdominal pain, decreased appetite, and nausea, most of which were mild to moderate.

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Clinical Context and Interpretation

Dysregulated cortisol and neuroinflammation have both been associated with ALS, and dazucorilant competitively antagonizes cortisol signaling.¹ DAZALS did not meet its primary end point of change in ALS Functional Rating Scale-Revised (ALSFRS-R) score over 24 weeks. Participants in the 300-mg arm did show improved OS, a secondary end point, at the end of the treatment period. At 1 year, the reduction in risk of death compared with placebo only was 84% (HR, 0.16; P = .0009).^2,3 Dazucorilant holds FDA fast track and orphan drug designations for ALS.²

The 2-year data are consistent with the survival signal reported at 1 year. The reductions in inflammatory markers point to a possible biological mechanism. Because the drug had no effect on ALSFRS-R, it is still unclear how a survival benefit would arise without measurable slowing of functional decline.

Limitations and Future Research

The OS analyses were exploratory, with the primary placebo-only comparator limited to 18 participants who elected not to cross over to active treatment, potentially introducing selection bias. Additionally, comparisons based on treatment duration were not randomized, and the abstract reported adverse events only from the open-label extension (OLE).¹

Corcept is currently conducting a dose-titration study aimed at improving the gastrointestinal tolerability of dazucorilant and informing the design of its planned phase 3 trial, which is expected to begin in 2027.^3,4 The upcoming trial will be critical in determining whether the observed survival benefit can be replicated under randomized conditions.

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REFERENCES
1. Ladha S, Sedarous M, Harms MB, et al. 2-year overall survival results from DAZALS: a phase 2, randomized controlled trial of dazucorilant, a selective glucocorticoid receptor modulator, in amyotrophic lateral sclerosis. Presented at: 2026 NEALS Annual Meeting; October 27-30, 2026; Clearwater, FL. Abstract 199.
2. Corcept presents results from phase 2 study of dazucorilant in patients with amyotrophic lateral sclerosis (ALS) at ENCALS 2025 annual meeting. News release. Corcept Therapeutics. June 5, 2025. Accessed November 6, 2026. https://www.businesswire.com/news/home/20250605516942/en
3. Corcept phase 2 study of dazucorilant demonstrates two-year overall survival benefit in patients with amyotrophic lateral sclerosis. News release. Corcept Therapeutics. April 30, 2026. Accessed November 6, 2026. https://www.businesswire.com/news/home/20260430885863/en
4. Corcept Therapeutics announces third quarter financial results and provides corporate update. News release. Corcept Therapeutics. November 3, 2026. Accessed November 6, 2026. https://www.businesswire.com/news/home/20261103499437/en